Development of Wet Adhesive Hydrogels to Correct Tracheomalacia

Tracheomalacia (TM) is a congenital disease seen commonly in infants. It is characterized as collapse, or narrowing of airway lumen during respiration, resulting from softness or weakness of cartilage rings and/or abnormality in tracheal muscle. The main clinical approach to solve TM is to correct the geometry of the malacic trachea and to prevent the airway collapse. Surgical interventions and stenting are commonly used treatment methods for TM. However, they have certain limitations. For example, surgical interventions are time consuming and require extensive surgical skills. On the other hand, stenting can cause stenosis, migration, erosion, and the rigidity of stents could prevent natural and dynamic neck movements in infants. Moreover, extraluminal stents needs to be fixed outside of the trachea with pexy sutures which causes trauma to the surrounding tissues. Therefore, current treatment options are not well-suited and there is no well-established method to treat TM effectively.<br/><br/>To overcome these limitations, a numerical model was developed to prove the hypothesis that airway collapse can be hindered by correcting the geometry of malacic trachea with the external mechanical support of an adhesive hydrogel patch. This <i>in silico</i> model showed that the application of an adhesive hydrogel patch helped to preserve the physiological shape of the trachea by constraining the tracheal membrane folding. Based on this study, we formulated a new adhesive hydrogel employing hydroxyethyl acrylamide (HEAam) and Polyethylene glycol dimethacrylate (PEGDM). We found that HEAam-based hydrogels provided robust wet adhesion on the tracheal surface thanks to the two-step polymerization approach, bonding firmly to the tissue surface much better than currently known adhesive hydrogels. We further used micro-CT and <i>ex vivo</i> measurements to prove the potential of the hydrogel patch to restrain the luminal collapse when it is wrapped to a malacic trachea extraluminally. Finally, we examined the durability and stability of the hydrogel with and without corporation of PEG-NHS in enzymatic and oxidative mediums. We observed that PEG-NHS increased adhesion performance, and decrease swelling and degradation behavior, which are key aspects to consider for biomaterials in long term. Therefore, this study, to be confirmed by in vivo studies, can overcome the current limitations and open the possibility of a new treatment in the difficult clinical situation of tracheomalacia in newborn.